Oxidative metabolic changes associated with phagocytosis are essential for the intracellular bacterial killing in neutrophils. Neutrophils from patients with chronic granulomatous disease have normal phagocytic capacity, but fail to produce superoxide and H202 during phagocytosis. As a result, they have impaired killing of ingested catalase-positive bacteria. The enzyme responsible for superoxide production and its location remain controversial. We propose to study: 1) the effect of sulfhydryl group inhibitors on the granular NADPH oxidase activity of human PMN. Both membrane penetrating and non-penetrating -SH group inhibitors will be used; 2) the effect of menadione sodium bisulfite on phagocytosis, phagocytosis associated oxidative metabolic changes and intracellular bacterial killing by PMN from normal individuals and patients with chronic granulomatous disease, and 3) metabolism and function of PMN from patients with suspected neutrophil dysfunction.